B3W2 Flashcards
Plasma v serum
serum = everything in blood without coagulation factors
plasma = water, proteins, nutrients, hormones, electrolytes, etc
Four main components of blood
erythrocytes, leukocytes, plasma, thrombocytes (platelets)
WNL viscosity
1.1 - 1.2
What is the normal volume of blood in an adult? a child?
7% of BW in adults, 10% of BW in children
What are the three layers of the hematocrit
- plasma
- buffy coat (WBC, platelets)
- RBC
Calculation for HCT
volume of RBC/ total volume
WNL hematocrit levels in males/females
males: 40-44%
females: 38-42%
Isolating serum vs isolating plasma
serum = allow for regular coagulation to sink to the bottom and then the serum will be the supernatent
plasma = calcium chelator blocks coagulation from occuring
Hematopoiesis chart (draw it out)
draw it out
What is the genetic regulator of EPO
HIFa
What is EPO and where is it produced
EPO is a hormone which is synthesized by the kidney and acts on progenitor cells in the bone marrow to stimulate RBC production
How would high altitudes and renal failure mean for EPO production
High altitudes lead to an overproduction of RBC, leading to elevated EPO
Renal failure will lead to a decrease EPO number synthesized leading to decrease in RBC and anemia
How do RBCs complete metabolism
-no mitochondria (no oxidative phosphorylation)
-uses glycolysis (90% of the time)
-uses pentose shunt pathway/hexose monophosphate shunt pathway
Which enzyme in the hexose shunt pathway leads to the most common enzymopathy?
glucose 6 phosphate dehydrogenase
Granulocytes v agranulocytes (which WBCs are which)
granulocytes: neutrophil, basophil, eosinophil
agranulocytes: monocytes, lymphocytes
WBC’s : what are they are what do they do
-Neutrophils (phagocytize bacteria)
-Lymphocytes (B cells and T cells)
-Monocytes (macrophages)
-Eosinophils (allergic reactions and parasites)
-Basophils (stimulates B cells and has role in allergic reactions)
Hemostasis definition
cessastion of bleeding through primary and secondary hemostasis (platelet plug then coagulation cascade)
Coagulation definition
clot formation as a form of hemostasis
anti-coagulation
taking a clot down, blocking clotting factors to prevent over clotting
fibrinolysis definition
breaking clots down
thrombosis definition
occlusion of a blood vessel
Substances that cause vasoconstriction in primary hemostasis
-serotonin, endothelian, TXA2
what is TXA2
platelet aggregator and vasoconstrictor
What is the purpose of placing direct pressure on a wound
it allows for a decrease in transmural pressure that leads to local vasoconstriction and decreases blood flow to area
Primary hemostasis (steps)
-Platelet plug formation
-Vasoconstriction
-Adhesion
–vWF released from endothelial cells during sheer stress, cytokine presence or hypoxia)
–vWB binds to Gp Ib on platelets allowing for platelets to bind to collagen, fibronectin and laminin on the endothelial cells
-Activation
–binding of collagen causes confirmational change on platelet receptors to trigger the Gq pathway in platelets leading to a high increase in intracellular Ca
–rise in Ca leads to exocytosis of dense storage and alpha granules hoding ADP, serotonin, TBXA2 to recruit platelets and vasoconstrict
-Aggregation
–recruited platelets aggregate to form a platelet thrombus
What are the two disorders of primary hemostasis
vWD - decreased vWF
Bernard Souiler syndrome - autosomal recessive disorder caused by Gp 1b deficiency
What are the intrinsic factors
XII, XI, IX, VIII
what are the extrinsic factors
III, VII
Common Pathway
X, V, I, II, XIII
(I = fibrinogen, II = thrombin) (XIII = fibrin stabilizing pathway)
draw out the coagulation cascade :)
sorry
Surface bound zymogens
XII, Prekallikrein, XI
Vitamin K dependent phospholipid bound zymogens
II, VII, IX, X
Cogaulation factors that are cofactors and substrates
HWMK, V, TF, VIII, fibrinogen
APTT vs PT vs thrombin time
APTT = intrinsic pathway
PT = extrinsic pathway
thrombin time = fibrinogen conversion time
What does an elevated APTT, PT or thrombin time mean clinically?
There is an increase for bleeding (default in the coagulation system)
Disorders of the intrinsic pathway that are associated with bleeding vs ones that are not
Not with bleeding: XII, HWMK, prekallikrein
all the rest are bleeding: XI, IX, VIII
What are the three main anticoagulants of the body
-Protein C/S
-antithrombin
-TFPI (tissue factor pathway inhibitors)
What factors does protein C/S inhibit
V, VIII
What factors do antithrombin inhibit
II, X
What factors does TFPI inhibit
VII, X
What is Factor V leiden
When factor 5 becomes resistant to protein C and S and leads to abnormal clot formation and inability to inhibit clot formation
Protein C vs Protein S
C = vit K dependent zymogen
S= vit K dependent enzyme regulated by C4b protein of the complement system
Physiology of inhibitor antithrombin
SERPIN - serine protease inhibitor
Thrombosis vs embolism
thrombosis = clot in vein
embolism = part of clot that enters circulation
Plasmin pathway
- plasmin to plasminogen to aid in the breakdown of stable fibrin into monomers of fibrin
-activated by tPA and uPA
-inhibited by PAI-1 and PAI-2 (higher pAI2 in pregnant women)
Electrical conduction pathway through the heart
SA node - AV node - bundle of HIs - purkinjee fibers - contractile myocytes
*aided through gap junctions and connexons)
Slow Pacemaker Cell Graph (what are the phases)
phase 4 - hyperpolarization/pacemaking
phase 0 - depolarization
phase 3 - repolarization
Slow pacemaking AP (where does it occur)
SA and AV nodes
Walk through the slow pacemaker graph
Phase 4: Funny channels (HCN4) are non specific cation channels which are open, K channels are deactivated and L type Ca channels are inactivated, with T type Ca channels turning on near depolarization
Phase 0: Ca influx for depolarization driving toward Ca eq potential
Phase 3: inactivation of Ca channels, activation of Ikr (HERG) and Iks channels (inward rectifying and delayed rectifier channels)
Fast AP graph (What are the stages)
Phase 0 = depolarization
Phase 1 = partial repolarization
Phase 2 = plateau
Phase 3 = repolarization
Phase 4 = hyperpolarization
Fast AP graph (where do they occur)
atrial and ventricular myocytes, Purkinjee fibers
Fast AP graph (go through the stages
Phase 0 = depolarization of Ca and Na channels
Phase 1 = inactivation of Na channels, activation of I(k,to) channels
Phase 2 = L type Ca channels are open (small #), and Ca release from RYR lead to holding, Na release through NCX1, K efflux caused by delayed rectifier K channels
Phase 3 = repolarization, decrease Ca channels open, increased K caused by Ikr (HERG) and IKs (delayed rectifier channels)
Phase 4 = hyperpolarization caused by KIR (inward rectifying K channel that is activated after removing intracellular Mg block), inactivation of Ca channels, allows for a constant influx and efflux of ions leading to stable Vm
Inward rectifier v outward rectifiers
Inward: during repolarization, allows for the maintaining of Vm, blocked by Mg
Outward: (HERG) pushes out for repolarization
Cardiac Pacemaker Regulation of slow action potentials (what are the two ways)
-sympathetic stimulation through adrenergic receptors
-parasympathetic innervation through muscarinic receptors
Sympathetic stimulation of cardiac pacemaker cells
-increases If channels (allows for a decreased phase 4 time)
-beta adrenergic receptors use the Gs pathway to increase cAMP, binding to If to stimulate L type Ca channels to decrease threshold, or to have PKA bind to Ca channels to modulate the channels and make them easier to open
Parasympathetic innervation
–Opens GIRK channels (Ik) to lead to increasing repolarization, increasing inward rectifying potassium channels, lowers potential during hyperpolarization
–inhibits cAMP to decrease funny current through the inhibition of AC and slows phase 4 depolarization to increase time
Difference between conduction velocity and pacemaking
conduction = speed of the propagation signal and depends on gap junctions (highest at ventricular and atrial myocytes, slowest at AV node)
pacemaking = speed of initiation of signal and depends on action potential propagation (pacemaking ability SA node >AV node > Purkinjee fibers)
What are the two refractory periods in the ventricular AP graph
effective refractory period (absolute)
relative refractory period
Why does effective refractory period happen and how
how: inactivation of Na channels
why: prevents ectopic heart beats and prevents tetanus
How does a relative refractory stimulus propogate
There is an action potential that leads to the Na and Ca reactivation and recovery of channels to depolarize again
EAD and DAD (what are they)
early after depolarization (phase 3)
delayed after depolarization (phase 4)
EAD (how do they happen)
EAD: prolonged action potentials, Long QT syndrome, quinidine (anti arrythmic drug that blocks Na channels to slow HR), hypokalemia, acidosis, hypoxia, bradycardia
these can lead to VTach
DAD (how do they happen)
DAD: spontaneous Ca release during diastole, increased intracellular Ca which increases SR reuptake and overflow, stimulation of the NCX which leads to bringing in Na to stimulate a depolarization (which leads to digitoxin toxicity and high levels of Ca
what are the waves of ECG
P wave = atrial depolarization
QRS = ventricular depolarization
S = ventricular repolarization
Give the values of the boxes of an ECG
little boxes = 0.04 seconds
big boxes = 0.2 seconds
5 boxes = 1 second
What are the hallmarks structures/intervals you are looking at when reading an ECG
-a P waves for every QRS
-positive leads on the left sided leads: I, aVL, V6
-positive leads on the inferior leads: II, III, avF
-Constant P-R intervals
-QRS intervals
How to calculate HR on ECG
2 methods:
-measure one R-R interval and count the number of small boxes and divide by 300
-count 6 seconds of ECG and multiply by 10
The two abnormalities which can be recognized on an ECG are:
anatomical and conduction abnormalities
1st degree block (what does it look like on ECG and anatomy)
ECG: constant prolonged PR interval
anatomy: slowing of the SA AV node conduction leading to slowing of conduction
2nd degree block (type 1, what does it look like on ECG, and anatomy)
Mobitz Type I (Weinchebach)
ECG: long, longer, longest PR interval then drop of a QRS
AV node: intermittentlty blocked
2nd degree block (type II, what does it look like on ECG, and anatomy)
Mobitz Type II
ECG: PR interval is constant then QRS drop
Anatomy: more permanent and can lead to type 3 block
3rd degree block (what does it look like on ECG and anatomy)
Complete conduction block (atria and ventricles are beating independently)
P waves are rhythmic and QRS are rhythmic but not together
If P and Q dont agree = you have 3rd degree
Bundle Branch Block (what does it look like, what lead to look at)
ECG:
(R) sided bundle block - seen in V1 lead with a wide QRS
(L) sided bundle block - seen in I lead with a wide (hat like) QRS complex
Wolf-Parkinson-White Syndrome (what does it look like on ECG)
delta wave with shortened PR interval showing that the ventricle is becoming “pre-excited”, accompanied by QRS
A-fib (what does it look like on ECG)
Afib = ectopic pacemakers or recirculation of electrical activity leading to ineffective contraction
ECG: lack of P waves, shows irregular QRS complexes
*increases risk of clotting
What is reentrant excitation
-there is a unidirectional block in the bundle of Kent/his which leads to the action potential to travel retrograde
V fib (on ECG)
uncoordinated ventricular depolarization leading to decrease in cardiac output and leading to Vtach, and then V-fib
Afib v Vfib
you can live with Afib , V fib is medical emergency and can lead to infarction
Preload - what is it
the volume of blood in ventricles preceding ejection , increasing preload increasing SV
Contractility - what is it
change in force at any given sarcomere - changes in contractility usually are due to Ca changes in the myocytes - increasing contractility increases SV
Afterload - what is it
the pressure the must be exerted by the ventricle to exceed atrial pressure for ventricular ejection
-increasing afterload, decreases SV
What is the area underneath the PV loop graph?
work exerted by blood
Isovolumetric contraction breaks down ATP and releases energy in the form of …….
tension heat
Go through the cardiac cycle and whether there are endocardial or epicardial fibers are shortening of lengthening
Isovolumetric contraction: endo shortening, epicardial stretching (clockwise)
ejection: endo and epi shortening (countrclockwise)
isovolumetric relaxation: endo shortening, epi stretching (clockwise)
ventricular filling: all stretching for filling (clockwise)
Anatomical difference of endocardial and epicardial fibers
epi are larger radius, stretch around the whole heart and have more torque
Go through the cardiac contraction cycle of systole
- excitation of the SA node
- AP depolarizes target cells via gap junctions
- spreads through T tubules to stimulate L type Ca channels to open
- Ca entry into the cell stimulates RYR to release Ca from SR (leading to CICR)
- Ca binds to troponin C
- Tropomyosin moves from the blocked state to open state
- Actin myosin bind
- cross bridging
Go through the cardiac relaxation cycle of diastole
Get rid of Ca
- Ca can be pumped into the ECF via NCX1, or MPCA
- SERCA reuptake
- Ca pumped into mitochondria
How does the SERCA pump activate
SERCA is usually inhibited by PLB, when phosphorylated PLB moves off of the SERCA activating it
How do beta 1 adrenergic receptors increase ionotrophy
They use the Gs pathway to increase cAMP, which increases PKA
PKA increase effects on the cell:
-phosphorylates L type Ca channels (more Ca into cell)
-phosphorylates Ryr (more Ca release)
-phosphorylates phospholamban (increases SERCA pump activity)
-phosphorylates TnI (dissociation of Ca from TnC leading to relaxation)
-phosphorylates MyBP-C which accelerates cross bridge recruitment and detachment to increase force generation
-speeds up power stroke and release of ADP
ALL INCREASE IONOTROPHIC EFFECTS = more contraction
How does force generation change in skeletal muscle vs cardiac muscle
skeletal: more motor innervation = more force
cardiac: changes in fiber and sarcomere length, changes in ionotrophy = more force
Frank Starling Law (preload) (afterload)
Increasing sarcomere length = More EDV = More preload = More SV = increased shortening velocity = More forceful contraction
Increased aferload = decrease shortening velocity = decreases SV = decreases CO
How does increasing the sarcomere length of cardiac muscles increase force generation (think Frank Starling)
increasing sarcomere length decreases the distance of cross bridges from each other, increases more strongly bound cross bridges, increases Ca affinity to TnC, increases probability of myosin and actin interaction
What is ESPVR
measures the end systolic pressure volume relationship
aids in determining contractility
A high slope of ESPVR vs a low one
high = high contractility
low = low contractility
What are factors that lead to higher contractility? lower?
high: adrenergic agonists, cardiac glycosides (that inhibit Na-K) high extracellular Ca, low extracellular Na, tachycardia
